This study reveals that ClpC, a Clp-family chaperone protein, acts as a negative regulator of competence in Streptococcus thermophilus by promoting ComX degradation. ComX is an alternative sigma factor essential for activating late competence genes required for natural DNA transformation. Researchers created deletion mutants and found that clpC-deficient strains showed significantly increased transformability and elevated late gene expression under conditions where ComX was expressed at low levels. Using plasmid-based reporter systems, they demonstrated that ClpC does not affect ComX transcription but instead regulates ComX post-translationally, likely through the ClpCP protease complex. When ComX is expressed at higher levels, the ClpCP complex becomes saturated and cannot prevent ComX accumulation. This mechanism differs from S. pneumoniae, which uses ClpEP for ComX degradation. The findings suggest ClpC prevents inappropriate competence development by degrading ComX when environmental signals for competence are weak, thereby providing temporal and spatial control over natural transformation.

Key findings

• ClpC acts as a negative regulator of competence by promoting ComX degradation through the ClpCP protease complex
• ClpC controls ComX levels post-translationally without affecting ComX transcription
• ClpC-deficient strains display increased transformability specifically when ComX is expressed at low basal levels
• ClpCP becomes saturated at higher ComX expression levels, allowing ComX accumulation and competence development
• This regulatory mechanism prevents S. thermophilus from entering competence inappropriately during weak environmental signals